Microchimica Acta

, Volume 182, Issue 5–6, pp 933–942 | Cite as

Voltammetric sensor for theophylline using sol–gel immobilized molecularly imprinted polymer particles

  • Ferdia Bates
  • Manel del Valle
Original Paper


Sensors incorporating molecularly imprinted polymers (MIPs) are feasible in concept though the reproducibility of such devices can be compromised by the large number of interdependent steps. For this reason, many researchers have focused on the synthesis of MIP particles only, not on their immobilization. Herein is presented a sol–gel based method for immobilization of unmodified MIP particles for use in an electrochemical sensor. The macroporous particles were prepared using precipitation-polymerization and imprinted with theophylline. The sol–gel was combined with graphite microparticles (50 μm) and the composite was deposited on the surfaced of an epoxy-graphite electrode. The sensor was then tested for its response to theophylline using differential pulse voltammetry. A limit of detection of 1 μM was observed and a relative standard deviation of 6.85 %. The electrode can be regenerated via a thermal washing process which was accompanied by an initial signal loss of 29.3 %. Any further regeneration caused a signal loss of 2.4 % only.

Graphical Abstract

A voltammetric sensor for the preferential detection of theophylline is prepared based on molecularly imprinted microspheres immobilized in a sol-gel layer. The use of precipitated polymer microparticles allows for the effective regeneration of the sensor using an acidic wash.


Molecularly imprinted polymers (MIP) Sol–gel Graphite Theophylline Differential pulse voltammetry 



This research was supported by the Research Executive Agency (REA) of the European Union under Grant Agreement number PITN-GA-2010-264772 (ITN CHEBANA), by the Ministry of Science and Innovation (MCINN, Madrid, Spain) through the project CTQ2010-17099 and by the Catalonia program ICREA Academia.


  1. 1.
    Mello LD, Kubota LT (2002) Review of the use of biosensors as analytical tools in the food and drink industries. Food Chem 77(2):237–256CrossRefGoogle Scholar
  2. 2.
    Kroger S, Turner APF, Mosbach K, Haupt K (1999) Imprinted polymer based sensor system for herbicides using differential-pulse voltammetry on screen printed electrodes. Anal Chem 71(17):3698–3702CrossRefGoogle Scholar
  3. 3.
    Wulff G (2013) Fourty years of molecular imprinting in synthetic polymers: origin, features and perspectives. Microchim Acta 180(15–16):1359–1370CrossRefGoogle Scholar
  4. 4.
    Whitcombe MJ, Kirsch N, Nicholls IA (2014) Molecular imprinting science and technology: a survey of the literature for the years 2004–2011. J Mol Recog 27(6):297–401CrossRefGoogle Scholar
  5. 5.
    Yan HY, Row KH (2006) Characteristic and synthetic approach of molecularly imprinted polymer. Int J Mol Sci 7(5–6):155–178CrossRefGoogle Scholar
  6. 6.
    Wulff G, Knorr K (2001) Stoichiometric noncovalent interaction in molecular imprinting. Bioseparation 10(6):257–276CrossRefGoogle Scholar
  7. 7.
    Yoshimi Y, Ohdaira R, Iiyama C, Sakai K (2001) “Gate effect” of thin layer of molecularly-imprinted poly (methacrylic acid-co-ethyleneglycol dimethacrylate). Sensors Actuators B Chem 73(1):49–53CrossRefGoogle Scholar
  8. 8.
    Sellergren B (1997) Noncovalent molecular imprinting: antibody-like molecular recognition in polymeric network materials. Trac-Trend Anal Chem 16(6):310–320CrossRefGoogle Scholar
  9. 9.
    Cormack PAG, Elorza AZ (2004) Molecularly imprinted polymers: synthesis and characterisation. J Chromatogr B 804(1):173–182CrossRefGoogle Scholar
  10. 10.
    Suryanarayanan V, Wu CT, Ho KC (2010) Molecularly imprinted electrochemical sensors. Electroanalysis 22(16):1795–1811CrossRefGoogle Scholar
  11. 11.
    Sellergren B, Shea KJ (1995) Origin of peak asymmetry and the effect of temperature on solute retention in enantiomer separations on imprinted chiral stationary phases. J Chromatogr A 690(1):29–39CrossRefGoogle Scholar
  12. 12.
    Barnes PJ (2010) Theophylline. Pharma 3(3):725–747Google Scholar
  13. 13.
    Alizadeh T, Ganjali MR, Zare M, Norouzi P (2010) Development of a voltammetric sensor based on a molecularly imprinted polymer (MIP) for caffeine measurement. Electrochim Acta 55(5):1568–1574CrossRefGoogle Scholar
  14. 14.
    Ebarvia BS, Binag CA, Sevilla F 3rd (2004) Biomimetic piezoelectric quartz sensor for caffeine based on a molecularly imprinted polymer. Anal Bioanal Chem 378(5):1331–1337CrossRefGoogle Scholar
  15. 15.
    Aranda M, Morlock G (2007) Simultaneous determination of caffeine, ergotamine, and metamizol in solid pharmaceutical formulation by HPTLC-UV-FLD with mass confirmation by online HPTLC-ESI-MS. J Chromatogr Sci 45(5):251–255CrossRefGoogle Scholar
  16. 16.
    Tzanavaras PD, Themelis DG (2007) Development and validation of a high-throughput high-performance liquid chromatographic assay for the determination of caffeine in food samples using a monolithic column. Anal Chim Acta 581(1):89–94CrossRefGoogle Scholar
  17. 17.
    Svorc L (2013) Determination of caffeine: a comprehensive review on electrochemical methods. Int J Electrochem Sci 8(4):5755–5773Google Scholar
  18. 18.
    Spataru N, Sarada BV, Tryk DA, Fujishima A (2002) Anodic voltammetry of xanthine, theophylline, theobromine and caffeine at conductive diamond electrodes and its analytical application. Electroanalysis 14(11):721–728CrossRefGoogle Scholar
  19. 19.
    Perez-Moral N, Mayes AG (2004) Comparative study of imprinted polymer particles prepared by different polymerisation methods. Anal Chim Acta 504(1):15–21CrossRefGoogle Scholar
  20. 20.
    Kan X, Zhao Q, Zhang Z, Wang Z, Zhu JJ (2008) Molecularly imprinted polymers microsphere prepared by precipitation polymerization for hydroquinone recognition. Talanta 75(1):22–26CrossRefGoogle Scholar
  21. 21.
    Adhikari B, Majumdar S (2004) Polymers in sensor applications. Prog Polym Sci 29(7):699–766CrossRefGoogle Scholar
  22. 22.
    Kriz D, Mosbach K (1995) Competitive amperometric morphine sensor-based on an agarose immobilized molecularly imprinted polymer. Anal Chim Acta 300(1–3):71–75CrossRefGoogle Scholar
  23. 23.
    Patel AK, Sharma PS, Prasad BB (2009) Electrochemical sensor for uric acid based on a molecularly imprinted polymer brush grafted to tetraethoxysilane derived sol–gel thin film graphite electrode. Mater Sci Eng C 29(5):1545–1553CrossRefGoogle Scholar
  24. 24.
    Prasad BB, Madhuri R, Tiwari MP, Sharma PS (2010) Electrochemical sensor for folic acid based on a hyperbranched molecularly imprinted polymer-immobilized sol–gel-modified pencil graphite electrode. Sensors Actuators B Chem 146(1):321–330CrossRefGoogle Scholar
  25. 25.
    Takagishi T, Klotz IM (1972) Macromolecule-small molecule interactions - introduction of additional binding-sites in polyethyleneimine by disulfide crosslinkages. Biopolymers 11 (2):483-&Google Scholar
  26. 26.
    Mujahid A, Lieberzeit PA, Dickert FL (2010) Chemical sensors based on molecularly imprinted sol–gel materials. Mater 3(4):2196–2217CrossRefGoogle Scholar
  27. 27.
    Ye L, Weiss R, Mosbach K (2000) Synthesis and characterization of molecularly imprinted microspheres. Macromolecules 33(22):8239–8245CrossRefGoogle Scholar
  28. 28.
    Ocaña C, Arcay E, del Valle M (2014) Label-free impedimetric aptasensor based on epoxy-graphite electrode for the recognition of cytochrome c. Sensors Actuators B Chem 191:860–865CrossRefGoogle Scholar
  29. 29.
    Patel AK, Sharma PS, Prasad BB (2008) Development of a creatinine sensor based on a molecularly imprinted polymer-modified sol–gel film on graphite electrode. Electroanalysis 20(19):2102–2112CrossRefGoogle Scholar
  30. 30.
    Sherrington DC (1998) Preparation, structure and morphology of polymer supports. Chem Commun 21:2275–2286CrossRefGoogle Scholar
  31. 31.
    Castell OK, Allender CJ, Barrow DA (2006) Novel biphasic separations utilising highly selective molecularly imprinted polymers as biorecognition solvent extraction agents. Biosens Bioelectron 22(4):526–533CrossRefGoogle Scholar
  32. 32.
    Mohamed MH, Wilson LD (2012) Porous copolymer resins: tuning pore structure and surface area with non reactive porogens. Nanomater 2(2):163–186CrossRefGoogle Scholar
  33. 33.
    Patel AK, Sharma PS, Prasad BB (2009) Electrochemical sensor for uric acid based on a molecularly imprinted polymer brush grafted to tetraethoxysilane derived sol–gel thin film graphite electrode. Mat Sci Eng C-Bio S 29(5):1545–1553CrossRefGoogle Scholar
  34. 34.
    Patel AK, Sharma PS, Prasad BB (2009) Voltammetric sensor for barbituric acid based on a sol-gel derivated molecularly imprinted polymer brush grafted to graphite electrode Int J Pharm 371(1–2):47–55Google Scholar
  35. 35.
    Liu J, Chaudhury MK, Berry DH, Seebergh JE, Osborne JH, Blohowiak KY (2006) Effect of surface morphology on crack growth at a sol–gel reinforced epoxy/aluminum interface. J Adhes 82(5):487–516CrossRefGoogle Scholar
  36. 36.
    Viana MM, Mohallem TDS, Nascimento GLT, Mohallem NDS (2006) Nanocrystalline titanium oxide thin films prepared by sol–gel process. Braz J Phys 36(3B):1081–1083CrossRefGoogle Scholar
  37. 37.
    Brittain HG (2007) Profiles of drug substances, excipients and related methodology: critical compilation of pKa values for pharmaceutical substances, vol 33. Academic, San Diego CAGoogle Scholar
  38. 38.
    Castell OK, Barrow DA, Kamarudin AR, Allender CJ (2011) Current practices for describing the performance of molecularly imprinted polymers can be misleading and may be hampering the development of the field. J Mol Recog 24(6):1115–1122CrossRefGoogle Scholar
  39. 39.
    Kirsch N, Hart JP, Bird DJ, Luxton RW, McCalley DV (2001) Towards the development of molecularly imprinted polymer based screen-printed sensors for metabolites of PAHs. Analyst 126(11):1936–1941CrossRefGoogle Scholar
  40. 40.
    Lai EPC, Fafara A, VanderNoot VA, Kono M, Polsky B (1998) Surface plasmon resonance sensors using molecularly imprinted polymers for sorbent assay of theophylline, caffeine, and xanthine. Can J Chem 76(3):265–273Google Scholar
  41. 41.
    Wang Z, Kang J, Liu X, Ma Y (2007) Capacitive detection of theophylline based on electropolymerized molecularly imprinted polymer. Int J Polym Anal Charact 12(2):131–142CrossRefGoogle Scholar
  42. 42.
    Niu J, Liu Z, Fu L, Shi F, Ma H, Ozaki Y, Zhang X (2008) Surface-imprinted nanostructured layer-by-layer film for molecular recognition of theophylline derivatives. Langmuir 24(20):11988–11994CrossRefGoogle Scholar
  43. 43.
    Kan X, Liu T, Zhou H, Li C, Fang B (2010) Molecular imprinting polymer electrosensor based on gold nanoparticles for theophylline recognition and determination. Microchim Acta 171(3–4):423–429CrossRefGoogle Scholar
  44. 44.
    Kim J-M, Lee U-H, Chang S-M, Park JY (2014) Gravimetric detection of theophylline on pore-structured molecularly imprinted conducting polymer. Sensors Actuators B Chem 200:25–30CrossRefGoogle Scholar
  45. 45.
    Tan X, Wang L, Li P, Gong Q, Liu L, Zhao D, Lei F, Huang Z (2012) Electrochemical sensor for the determination of theophylline based on molecularly imprinted polymer with ethylene glycol maleic rosinate acrylate as cross-linker. Acta Chim Sin 70(9):1088–1094CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Sensors and Biosensors Group, Department of ChemistryUniversitat Autònoma de BarcelonaBarcelonaSpain

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